2BAP

Crystal structure of the N-terminal mDia1 Armadillo Repeat Region and Dimerisation Domain in complex with the mDia1 autoregulatory domain (DAD)

2BAP の概要

• エントリーDOI: 10.2210/pdb2bap/pdb
• 関連するPDBエントリー: 1z2c 2bnx
• 分子名称: Diaphanous protein homolog 1 (2 entities in total)
• 機能のキーワード: armadillo repeats, all helical, signaling protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• 細胞内の位置: Cell membrane : O08808 O08808
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 85988.90

構造登録者

Lammers, M.,Rose, R.,Scrima, A.,Wittinghofer, A. (登録日: 2005-10-14, 公開日: 2006-03-07, 最終更新日: 2023-08-23)

主引用文献

Lammers, M.,Rose, R.,Scrima, A.,Wittinghofer, A.
The regulation of mDia1 by autoinhibition and its release by Rho*GTP.
Embo J., 24:4176-4187, 2005

PubMed Abstract: Formins induce the nucleation and polymerisation of unbranched actin filaments via the formin-homology domains 1 and 2. Diaphanous-related formins (Drfs) are regulated by a RhoGTPase-binding domain situated in the amino-terminal (N-terminal) region and a carboxy-terminal Diaphanous-autoregulatory domain (DAD), whose interaction stabilises an autoinhibited inactive conformation. Binding of active Rho releases DAD and activates the catalytic activity of mDia. Here, we report on the interaction of DAD with the regulatory N-terminus of mDia1 (mDia(N)) and its release by Rho*GTP. We have defined the elements required for tight binding and solved the three-dimensional structure of a complex between an mDia(N) construct and DAD by X-ray crystallography. The core DAD region is an alpha-helical peptide, which binds in the most highly conserved region of mDia(N) using mainly hydrophobic interactions. The structure suggests a two-step mechanism for release of autoinhibition whereby Rho*GTP, although having a partially nonoverlapping binding site, displaces DAD by ionic repulsion and steric clashes. We show that Rho*GTP accelerates the dissociation of DAD from the mDia(N)*DAD complex.

PubMed: 16292343
DOI: 10.1038/sj.emboj.7600879

実験手法

X-RAY DIFFRACTION (3.3 Å)